Clinical Trials Register

Summary
EudraCT Number:	2008-005041-33
Sponsor's Protocol Code Number:	MAG111539
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-05-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2008-005041-33

A.3

Full title of the trial

A Single-Blind Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Repeat Doses of GSK249320 in Patients With Stroke.

A.4.1

Sponsor's protocol code number

MAG111539

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Research & Development Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	GSK249320
D.3.2	Product code	GSK249320
D.3.4	Pharmaceutical form	Intravenous infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	GSK249320
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	humanised monoclonal antibody

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Intravenous infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with Stroke.

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10042244
E.1.2	Term	Stroke

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of two repeat IV doses of GSK249320 in subjects with stroke

E.2.2

Secondary objectives of the trial

1.To evaluate immunogenicity of two repeat IV doses of GSK249320 in subjects with stroke.
2.To evaluate the pharmacokinetics (PK) of two repeat IV doses of GSK249320 in subjects with stroke.
3.To characterize functional and neurophysiological outcome measures in subjects with stroke.
4.To explore any pharmacodynamic (PD) effects of GSK249320 on functional and electrophysiological outcome measures in subjects with stroke.
5. To explore PK-PD relationships between exposure and functional endpoints.
6. To explore the status of blood brain barrier integrity in the study population.
7. To explore the oligodendrocyte protection property of GSK249320.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A subject will be eligible for inclusion in this study only if all of the following criteria
apply:
1. Have a confirmed diagnosis of stroke according to the World Health Organization
definition which is, ‘a rapid onset event of vascular origin reflecting a focal
disturbance of cerebral function, excluding isolated impairments of higher function,
and persisting longer than 24 hours [World Health Organization, 1989].
2. Stroke onset must be within the last 24-72 hours. Time of stroke onset is defined as the time at which the patient/relative is first aware of the stroke deficit. For patients who awake with deficits, or who are found unconscious, the time of onset is defined as the time at which they were last known to be symptom free.
3. Have a stroke that is either:
a. Radiologically confirmed to be ischemic and supratentorial. The diameter of the ischemic lesion is >15mm in any single direction or the volume is >4cc.
OR
b. Radiologically confirmed to be an intracerebral hemorrhage that is supratentorial, deep (i.e., blood must not directly contact cerebral cortex) and with minimal or no intraventricular extension. The Intracerebral Hemorrhage (ICH) score must be 0-2 and is calculated based on age, Glasgow Coma Scale score and the initial CT or MRI findings for the index stroke. See the SPM for the full calculation procedure.
4. Have a total NIHSS score of 3-21.
5. Have an upper and/or lower limb deficit defined as:
a. Score of 1-3 on the NIHSS Motor Arm question (question #5), and palpable and
observable voluntary extension or flexion of the fingers.
AND/OR
b. Score of 1-3 on the NIHSS Motor Leg question (question #6)
6. Aged 18-90, inclusive.
7. Reasonable likelihood of receiving standard physical, occupational and speech
rehabilitation therapy as indicated for the post stroke deficits.
8. Reasonable likelihood of receiving both doses of Investigational Product.
9. Be able to provide written and dated informed consent. Where the subject is unable to give consent, consent may be obtained from the subject’s legally authorized representative in accordance with national legislation and local ethics committee guidelines. When able to do so, the subject should be re-consented to continue in the study in the case where the consent was obtained from the legal representative in the first instance.
10. Male subjects and females of non-child-bearing potential are allowed to participate in this study.
11. Females of child-bearing potential are also allowed to participate in this study
provided they are using a contraceptive method with a failure rate of <1%. See
Section 7.1 for more information on allowable methods of contraception.

E.4

Principal exclusion criteria

A subject will not be eligible for inclusion in this study if any of the following criteria
apply:
1. History of a previous symptomatic stroke within 3 months prior to study entry.
2. Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke Rankin score of >2.
3. Presence of depression that is active and not adequately controlled such that it
interferred with major activities of daily living immediately prior to the current
stroke.
4. Subjects who are not alert or are unresponsive as defined by a score of 2 or 3 on the NIHSS Level of Consciousness question (question #1a).
5. Presence of significant aphasia likely to confound or interfere with completion of the study assessments.
6. Presence of peripheral neuropathy, including diabetic neuropathy, which is clinically active and symptomatic at time of screening.
7. Presence of neurological or psychiatric disease, such as dementia or mild cognitive impairment, prior to study entry that is likely to confound clinical evaluations
8. Presence of a demyelinating disease, such as multiple sclerosis.
9. Evidence of other chronic co-morbid conditions or unstable acute systemic illnesses which, in the opinion of the investigator, could shorten the subject’s survival or limit his/her ability to complete the study
10. History of sensitivity to heparin or heparin-induced thrombocytopenia.
11. Presence of QTc > 500 msec; or uncorrected QT >600msec (machine or manual over-read) on baseline ECG. If bundle branch block is present, then QTc must not be > 530 msec.
12. Contraindication to TMS, such as:
• have metal present, such as hardware or plate on the scalp in the area to which TMS will be applied, implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials
• occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan.
• concomitant use of drugs that substantially lower seizure threshold (e.g., tricyclic antidepressants and neuroleptics)
• known history of seizures or epilepsy
• brain tumor, recent brain injury (within 5 years) associated with definite loss of consciousness, or any history of brain surgery
• other contraindications per local hospital practice
13. Contraindication to MRI, such as:
• have metal present, such as implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials, permanent tattooed metallic eye-liner
• occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan.
• claustrophobia
• other contraindications per local hospital practice
14. Participation in any investigational rehabilitation paradigm targeting stroke recovery during the duration of this study.
15. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
16. History of sensitivity to GSK249320, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
17. Pregnant females as determined by positive urine hCG test at screening or prior to dosing.
18. Lactating females.
19. Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol.

E.5 End points

E.5.1

Primary end point(s)

Adverse events (AEs), vital signs, physical examination (incl. full neurological exam.), 12-lead ECGs, nerve conduction tests (NCTs), magnetic resonance imaging (MRI) and clinical laboratory tests.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

As this is the first safety study of GSK249320 in ischaemic stroke, further safety data will be required to enable longer term use of GSK249320 in patients with stroke.
Consequently subjects will not receive any investigational product after completion of the study. However, subjects may continue to receive or start any standard of care therapies such as physical, occupational, or speech rehabilitation for their post stroke deficits. View section 9.4 of the protocol for further information.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2009-07-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-06-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-01-31

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